Richard D. Pearson

Rates of Needle-Stick Injury Caused by Various Devices in a University Hospital

We identified characteristics of devices that caused needle-stick injuries in a university hospital over a 10-month period. Hospital employees who reported needle sticks were interviewed about the types of devices causing injury and the circumstances of the injuries. Of 326 injuries studied, disposable syringes accounted for 35 percent, intravenous tubing and needle assemblies for 26 percent, prefilled cartridge syringes for 12 percent, winged steel-needle intravenous sets for 7 percent, phlebotomy needles for 5 percent, intravenous catheter stylets for 2 percent, and other devices for 13 percent. When the data were corrected for the number of each type of device purchased, disposable syringes had the lowest rate of needle sticks (6.9 per 100,000 syringes purchased). Devices that required disassembly had rates of injury of up to 5.3 times the rate for disposable syringes. One third of the injuries were related to recapping. Competing hazards were often cited as reasons for recapping. They included the risk of disassembling a device with an uncapped, contaminated needle and the difficulty of safely carrying several uncapped items to a disposal box in a single trip. New designs could provide safer methods for covering contaminated needles. Devices should be designed so that the workers hands remain behind the needle as it is covered, the needle should be covered before disassembly of the device, and the needle should remain covered after disposal. Such improvements could reduce the incentives for recapping needles and lower the risk of needle-stick injuries among health care workers.

The Practice of Travel Medicine: Guidelines by the Infectious Diseases Society of America

David R. Hill, Charles D. Ericsson, Richard D. Pearson, Jay S. Keystone, David O. Freedman, Phyllis E. Kozarsky, Herbert L. DuPont, Frank J. Bia, Philip R. Fischer, and Edward T. Ryan National Travel Health Network and Centre and Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, England; Department of Medicine, University of Toronto, and Center for Travel and Tropical Medicine, Toronto General Hospital, Toronto, Ontario, Canada; Department of Internal Medicine, Clinical Infectious Diseases, University of Texas Medical School at Houston, Department of Internal Medicine, St. Luke’s Hospital, and Center for Infectious Diseases, University of Texas at Houston School of Public Health, and Department of Medicine, Baylor College of Medicine, Houston, Texas; Departments of Medicine and Pathology, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia; Departments of Medicine and Epidemiology, Division of Geographic Medicine, University of Alabama at Birmingham, Birmingham; Department of Medicine, Infectious Diseases, Emory University School of Medicine, and 16 Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia; Department of Medicine and Laboratory Medicine, Yale Medical School, New Haven, Connecticut; Department of Pediatrics, Division of General Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, and Mayo Eugenio Litta Children’s Hospital, Mayo Clinic, Rochester, Minnesota; and Department of Medicine, Division of Infectious Diseases, Harvard Medical School, Harvard School of Public Health, and Tropical and Geographic Medicine Center, Massachusetts General Hospital, Boston, Massachusetts

An urban outbreak of visceral leishmaniasis in Natal, Brazil

The epidemiological pattern of visceral leishmaniasis in north-eastern Brazil is changing. The disease was typically seen in rural, endemic areas, but is now occurring as an epidemic in the city of Natal where 316 cases have been reported since 1989; 49% were in children less than 5 years of age. The principle clinical and laboratory findings were weight loss, fever, hepato-splenomegaly, anaemia, leucopenia and hypergammaglobulinaemia. Elevated transaminases and hyperbilirubinaemia were also observed. The diagnosis was confirmed in 87% of cases by identifying amastigotes in aspirates from bone marrow or spleen. Five isolates were identified as Leishmania (L.) chagasi by isoenzyme analysis. The mortality rate was 9%; all deaths occurred during the first week in hospital. One person had concurrent human immunodeficiency virus infection. Among 210 household contacts and neighbours of patients from the endemic area examined for evidence of L. (L.) chagasi infection, 6 additional cases of visceral leishmaniasis were diagnosed. Thirty-eight percent of house-mates and neighbours gave a positive Montenegro skin test reaction, indicating prior subclinical infection.

Risk of needle stick and sharp object injuries among medical students

BACKGROUND Much is known about sharp object and needle stick injuries among employee health care workers, but relatively little attention has been directed to exposures among medical students. METHOD The frequency and mechanisms of needle stick and sharp object injuries were determined retrospectively by surveying students in their fourth year of medical school. Students were questioned about the number of percutaneous injuries that they had sustained during their clinical years. Descriptive information was collected on their most recent injury. RESULTS Of 137 students in the class, 106 (77%) responded. Thirty-five (33%) of the students who responded sustained one or more injuries; 24 (69%) were injured while on a surgical service, and 60% of the injuries occurred in an operating room. Suturing was the procedure most frequently associated with injury. In 34% of cases, the injury was caused by a needle or device being used by another person. The most frequent site of injury was the hand (97%). Ninety-four percent of students were wearing gloves at the time of the injury. None of the injuries was associated with recapping needles. Only 43% of students reported their injuries to proper authorities. CONCLUSION Medical students frequently sustain needle stick and sharp object injuries during their clinical training. Concerted efforts are needed to protect them.

Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype–phenotype association study

BACKGROUND As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. METHODS We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin-piperaquine. We then did a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin-piperaquine treatment. FINDINGS Piperaquine IC50s increased significantly from 2011 to 2013 in three Cambodian provinces (2011 vs 2013 median IC50s: 20·0 nmol/L [IQR 13·7-29·0] vs 39·2 nmol/L [32·8-48·1] for Ratanakiri, 19·3 nmol/L [15·1-26·2] vs 66·2 nmol/L [49·9-83·0] for Preah Vihear, and 19·6 nmol/L [11·9-33·9] vs 81·1 nmol/L [61·3-113·1] for Pursat; all p≤10-3; Kruskal-Wallis test). Genome-wide analysis of SNPs identified a chromosome 13 region that associates with raised piperaquine IC50s. A non-synonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin-piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin 2 and plasmepsin 3 genes on chromosome 14 also associate with raised piperaquine IC50s. After adjusting for covariates, both exo-E415G and plasmepsin 2-3 markers significantly associate (p=3·0 × 10-8 and p=1·7 × 10-7, respectively) with decreased treatment efficacy (survival rates 0·38 [95% CI 0·25-0·51] and 0·41 [0·28-0·53], respectively). INTERPRETATION The exo-E415G SNP and plasmepsin 2-3 amplification are markers of piperaquine resistance and dihydroartemisinin-piperaquine failures in Cambodia, and can help monitor the spread of these phenotypes into other countries of the Greater Mekong subregion, and elucidate the mechanism of piperaquine resistance. Since plasmepsins are involved in the parasites haemoglobin-to-haemozoin conversion pathway, targeted by related antimalarials, plasmepsin 2-3 amplification probably mediates piperaquine resistance. FUNDING Intramural Research Program of the US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and UK Department for International Development.

Praziquantel: A major advance in anthelminthic therapy

Praziquantel recently has been approved in the United States for use against a broad range of trematodes and cestodes. The drug is highly effective against all Schistosoma species that infect humans as well as other flukes and tapeworms, including the larval stage of Taenia solium, which causes cysticercosis. In addition, praziquantel is relatively nontoxic, well accepted by patients, and can be given orally in one dose or several doses in a single day. Praziquantel lowers or abolishes the threshold for treating persons with these infections, and, if costs can be contained, may help in the global control of serious systemic helminthic infections.

An Emerging Peri-Urban Pattern of Infection with Leishmania chagasi, the Protozoan Causing Visceral Leishmaniasis in Northeast Brazil

Peri-urban visceral leishmaniasis (VL) caused by Leishmania chagasi is emerging in a new epidemiologic pattern in Brazilian cities. We studied peri-urban VL in endemic neighborhoods surrounding Natal, Brazil, identified through hospitalized individuals with VL. Clinical and environmental information obtained for 1106 members of 216 families living in endemic neighborhoods enabled us to identify 4 groups: VL: individuals with current or prior symptomatic visceral leishmaniasis (n=135); DTH+: individuals with positive delayed-type hypersensitivity response with no history of VL (n=390); Ab+: individuals with negative DTH response and seropositive (n=21); DTH−: individuals with negative DTH and seronegative (n=560). The mean±SD age of VL was 9.3±12.3 y. The gender distribution was nearly equal below age 5, but skewed toward males at higher ages. Acutely infected VL subjects had significantly lower hematocrits, neutrophils, and eosinophils than other categories. AB+ subjects also had lower eosinophil counts than others, a possible immune marker of early infection. VL was not associated with ownership of dogs or other animals, raising the question whether the reservoir differs in peri-urban settings. This new pattern of L. chagasi infection enables us to identify epidemiological and host factors underlying this emerging infectious disease.

Pentamidine for the Treatment of Pneumocystis carinii Pneumonia and Other Protozoal Diseases

Pentamidine isethionate, discovered to have antiprotozoal activity in 1938, has recently been approved in the United States for the treatment of Pneumocystis carinii pneumonia. Despite frequent adverse reactions, which are at times life-threatening, pentamidine remains an important alternative to trimethoprim-sulfamethoxazole for the treatment of P. carinii pneumonia in patients with a history of allergy to sulfonamides or who have severe reactions or a lack of response to treatment with trimethoprim-sulfamethoxazole. Although not approved for other indications, pentamidine has been shown to be effective when used prophylactically against Trypanosoma brucei gambiense, the cause of West African sleeping sickness, as well as for treatment of the early hemolymphatic stage of that disease, and for treatment of some forms of leishmaniasis.

The South Asian genome.

The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the worlds population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1–HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed Pcombined = 2.76 × 10−17 and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30–1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1–HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1–HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species.